Identification and pharmacome analysis of receptor phenotypes originated from a single gene

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Every protein such as a receptor or enzyme is biosynthesized according to one corresponding gene. However, after expression, proteins may be frequently modified by many factors innative cells and tissues, so that these proteins no longer exhibit a single property. We have proposed t hat all of such proteins occurring in native tissues are designated as the `pharmacome'. In this study, we performed pharmacome analysis of α1-adrenoceptor (AR). At first, we found a unique a1-AR mediating adrenergic contraction in lower urinary tract and named as a1 L-AR because of its low affinity for prazosin. The a1 L-AR was identified by binding approach with intact tissue segments but not with membrane preparations. Thus, aft-AR converted to a1A-AR up on homogenization, suggesting a possible relationship between the both a1-ARs. Then we examined the effects of knockout (KO) of a1 -ARs. In wild-type, a1B-KO and a1D-KO mice, a1 L-AR was identified in functional and binding studies. However, in a1 A-K0 mice, not only a1A-AR but also a1L-AR was abolished. From these results it is concluded that both a1A-and a 1L-ARs are derived from a1A-AR gene, indicating that different phenotypes are expressed from a single gene.